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Eur J Med Genet. 2019 Mar;62(3):210-216. doi: 10.1016/j.ejmg.2018.07.016. Epub 2018 Jul 18.

Clinical report of 8 patients with 49,XXXXY syndrome: Delineation of the facial gestalt and depiction of the clinical spectrum.

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Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany. Electronic address:
Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
Institute of Human Genetics, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Klinik für Pädiatrie m.S. Endokrinologie und Diabetologie, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Kinderklinik, Sozialpädiatrisches Zentrum, Alb Fils Kliniken, Göppingen, Germany.
Dental Center, Baden, Switzerland.
Dental Practice in the Dental-Medical Training Center, Stuttgart, Germany.
Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Switzerland.


49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome. Cognitive impairment with expressive language deficits in combination with developmental and speech dyspraxia are cardinal symptoms. Testicular insufficiency becomes apparent during adolescence. Neurological, musculoskeletal, genital, orthodontic and immunological anomalies are common and a higher incidence of congenital malformations has been described. Here we show the evolving clinical and facial phenotype of eight boys and men with 49,XXXXY, demonstrating an increasingly perceptible distinct facial gestalt over time. In addition, almost all patients had muscular hypotonia, radioulnar synostosis, white matter anomalies, fifth-finger clinodactyly, recurrent respiratory infections in early childhood and teeth anomalies. IQ scores ranged between 40 and 70. Though many boys showed short stature at some point in early childhood, most outgrew it. As more long term data of boys and men with 49,XXXXY become available, parents of affected boys can be counseled more specifically as to the expected course and spectrum of this rare chromosomal disorder. Moreover, the multidisciplinary support can be optimized und unnecessary diagnostics avoided.


49,XXXXY; Sex chromosome pentasomy; White matter lesions

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